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Collagen‐derived dipeptide, proline‐hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts
Author(s) -
OHARA Hiroki,
ICHIKAWA Satomi,
MATSUMOTO Hitoshi,
AKIYAMA Minoru,
FUJIMOTO Norihiro,
KOBAYASHI Takashi,
TAJIMA Shingo
Publication year - 2010
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2010.00827.x
Subject(s) - hyaluronic acid , hyaluronan synthase , cell growth , microbiology and biotechnology , chemistry , hydroxyproline , gene knockdown , extracellular matrix , fibroblast , biochemistry , biology , in vitro , apoptosis , genetics
Orally ingested collagen undergoes degradation to small di‐ or tripeptides, which are detected in circulating blood 2 h after ingestion. The influence of collagen‐derived peptides on dermal extracellular matrix components and cell proliferation was studied using cultured human dermal fibroblasts. Of the various collagenous peptides tested here, the dipeptide proline‐hydroxyproline (Pro‐Hyp) enhanced cell proliferation (1.5‐fold) and hyaluronic acid synthesis (3.8‐fold) at a dose of 200 nmol/mL. This was concomitant with a 2.3‐fold elevation of hyaluronan synthase 2 ( HAS2 ) mRNA levels. Small interfering RNA (siRNA)‐mediated knockdown of the HAS2 gene in human dermal fibroblasts inhibited Pro‐Hyp‐induced HAS2 mRNA transcription and cell mitotic activity. Addition of genistein or H7, a protein kinase inhibitor, abolished the Pro‐Hyp‐induced HAS2 mRNA stimulation. Pro‐Hyp elevated phosphorylation of signal transducer and activator of transcription 3 (STAT3) within a short time period (60 min). These results suggest that Pro‐Hyp stimulates both cell mitotic activity and hyaluronic acid synthesis, which is mediated by activation of HAS2 transcription.